The purpose of this research proposal is to study in vivo and in vitro selected aspects of the hormonal regulation of calcium and skeletal metabolism. This will be accomplished by clinical and experimental studies of the biosynthesis, secretion, metabolism, and biological effects of the three calcitropic hormones - parathyroid hormone (PTH), calcitonin (CT), and vitamin D. Emphasis will be placed on interactions among these three hormones as well as their interactions with other hormones, such as gonadal and adrenal steroids, and other factors, such as age and sex, which regulate mineral metabolism. Hormone measurements will be made by competitive-binding assays, receptor assays, and bioassays. Mineral measurements will be made by ionic as well as non-ionic methods. Skeletal assessment will be conducted by radiographic, biochemical, and immunochemical procedures. In vivo studies will be conducted in humans and experimental animals during provocative tests of hormone secretion in physiological and pathophysiological states. In vitro studies will be conducted with preparations of hormone-producing cells and preparations of the target organs of the calcitropic hormones, especially bone. These studies should help to define the hormonal dynamics which underlie normal and abnormal bone mineral metabolism.